Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
Abstract Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participatio...
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2017-08-01
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doaj-9cd2b9c633a74c8184f98b09354dec722020-12-08T01:32:52ZengNature Publishing GroupScientific Reports2045-23222017-08-017111310.1038/s41598-017-07380-9Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sitesVirginia C. Rodríguez-Cortez0Paloma Martínez-Redondo1Francesc Català-Moll2Javier Rodríguez-Ubreva3Antonio Garcia-Gomez4Ganesh Poorani-Subramani5Laura Ciudad6Henar Hernando7Arantxa Pérez-García8Carlos Company9José M. Urquiza10Almudena R. Ramiro11Javier M. Di Noia12Alejandro Vaquero13Esteban Ballestar14Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin Biology Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Institut de Recherches Cliniques de Montréal, Division of Immunity and Viral InfectionsChromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)B Cell Biology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)B Cell Biology Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Institut de Recherches Cliniques de Montréal, Division of Immunity and Viral InfectionsChromatin Biology Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Abstract Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites.https://doi.org/10.1038/s41598-017-07380-9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Virginia C. Rodríguez-Cortez Paloma Martínez-Redondo Francesc Català-Moll Javier Rodríguez-Ubreva Antonio Garcia-Gomez Ganesh Poorani-Subramani Laura Ciudad Henar Hernando Arantxa Pérez-García Carlos Company José M. Urquiza Almudena R. Ramiro Javier M. Di Noia Alejandro Vaquero Esteban Ballestar |
spellingShingle |
Virginia C. Rodríguez-Cortez Paloma Martínez-Redondo Francesc Català-Moll Javier Rodríguez-Ubreva Antonio Garcia-Gomez Ganesh Poorani-Subramani Laura Ciudad Henar Hernando Arantxa Pérez-García Carlos Company José M. Urquiza Almudena R. Ramiro Javier M. Di Noia Alejandro Vaquero Esteban Ballestar Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites Scientific Reports |
author_facet |
Virginia C. Rodríguez-Cortez Paloma Martínez-Redondo Francesc Català-Moll Javier Rodríguez-Ubreva Antonio Garcia-Gomez Ganesh Poorani-Subramani Laura Ciudad Henar Hernando Arantxa Pérez-García Carlos Company José M. Urquiza Almudena R. Ramiro Javier M. Di Noia Alejandro Vaquero Esteban Ballestar |
author_sort |
Virginia C. Rodríguez-Cortez |
title |
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites |
title_short |
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites |
title_full |
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites |
title_fullStr |
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites |
title_full_unstemmed |
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites |
title_sort |
activation-induced cytidine deaminase targets suv4-20-mediated histone h4k20 trimethylation to class-switch recombination sites |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
description |
Abstract Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites. |
url |
https://doi.org/10.1038/s41598-017-07380-9 |
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